BBBD Followed By Methotrexate and Carboplatin With or Without Trastuzumab in Treating Women With Breast Cancer That Has Spread to the Brain

• Status: Withdrawn
• Trial end date: 2013-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

RATIONALE: Osmotic blood-brain barrier disruption uses certain drugs, such as mannitol, to open the blood vessels around the brain and allow tumor-killing substances to be carried directly to the brain. Drugs used in chemotherapy, such as methotrexate and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Trastuzumab may also help methotrexate and carboplatin work better by making tumor cells more sensitive to the drugs. Giving osmotic blood-brain barrier disruption together with methotrexate, carboplatin, and trastuzumab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of carboplatin when given together with methotrexate and trastuzumab after mannitol in treating women with breast cancer that has spread to the brain.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: OHSU Knight Cancer Institute
• Collaborator: National Cancer Institute (NCI)
• Treatments: Carboplatin; Methotrexate; Sodium thiosulfate; Trastuzumab

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed breast cancer metastatic to the central nervous system (as documented by brain biopsy, cytology [analysis from cerebrospinal fluid]) OR radiographic evidence of brain metastasis with a diagnosis of systemic breast cancer

• Patients must have stable or no systemic disease as determined by a CT scan of the chest, abdomen, and pelvis

• HER2-positive or -negative disease by fluorescent in situ hybridization (FISH) or immunohistochemistry

• Patients with HER2-positive disease and signs of intracranial herniation and/or spinal block may first undergo intraarterial chemotherapy off study (with carboplatin, methotrexate, and trastuzumab [Herceptin®] by the same routes used on study) until radiographically shown to be safe to undergo blood brain barrier disruption, at which point they may be enrolled in the study

• Hormone receptor status not specified

PATIENT CHARACTERISTICS:

• Female

• Menopausal status not specified

• ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

• Life expectancy > 6 weeks

• Hematocrit ≥ 25%

• WBC ≥ 2,500/mm³

• Absolute neutrophil count ≥ 1,200/mm³

• Platelet count ≥100,000/mm³

• Creatinine clearance ≥ 50 mL/min (eligible for full-dose methotrexate) (30-49 mL/min allowed for patients receiving reduced-dose methotrexate)

• Bilirubin ≤ 2.0 times upper limit of normal

• LVEF normal by echocardiogram or MUGA

• Adequate pulmonary and cardiac function to tolerate general anesthesia as determined by physical examination and history

• No New York Heart Association class III-IV heart disease

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No known allergy to trastuzumab (HER2-positive patients), carboplatin, methotrexate, or sodium thiosulfate

• No hepatitis B or C positivity

• No uncontrolled intercurrent illness including, but not limited to, any of the following:

• Ongoing or active infection (e.g., HIV)

• Symptomatic congestive heart failure

• Unstable angina pectoris

• Cardiac arrhythmia

• Psychiatric illness or social situations that would limit compliance with study requirements

PRIOR CONCURRENT THERAPY:

• Prior surgery or biopsy allowed

• Prior chemotherapy and radiation therapy for metastatic breast cancer allowed

• No radiation or cytotoxic chemotherapy within the past 4 weeks (except trastuzumab or hormone therapy that has been part of the patient's ongoing treatment [e.g., aromatase inhibitors for estrogen receptor positive patients])

• No noncytotoxic regimens (e.g., targeted oral agents) within the past 2 weeks

• No investigational agents within the past 4 weeks

• No other concurrent anticancer agents or therapies